Microorganisms have been employed in the industrial production of a broad range of useful substances. For example, microorganisms have been used to produce not only alcoholic beverages and foods such as miso (fermented soy paste) and shoyu (soy sauce), but also amino acids, organic acids, nucleic acid-related substances, antibiotics, sugars, lipids, proteins, and many other types of substances. Use of such substances can be found in a wide range of fields, encompassing foods, pharmaceuticals, daily necessaries such as detergents and cosmetics, and a variety of raw materials for producing items through chemical processes.
One important issue in the industrial production of useful substances through use of microorganisms is improvement in productivity. Thus, as a measure therefor, cultivation of substance-producing microorganisms has been performed through traditional genetic techniques such as mutation. In particular, thanks to progress in microbial genetics and biotechnology, such cultivation of substance-producing microorganisms is now being carried out more efficiently than ever by use of a genetic technologies such as a genetic engineering technology, giving rise to development of host microorganisms useful for genetic recombination. For example, there has been developed a microorganism strain, which resulted from improvement of a microorganism strain Bacillus subtilis Marburg No. 168 that had been acknowledged to be safe and excellent.
Microorganisms harbor a diversity of genes, so that they can adapt themselves to environmental changes in the natural kingdom. Therefore, substance productivity of microorganisms cannot necessarily be said to be efficient in terms of industrial production of proteins or similar substances employing limited types of production medium.
Also, concerning certain types of microorganisms, there have been established strains in which genes participating in early stage sporulation are singly deleted or inactivated. However, these strains will not be said to be sufficiently improved in productivity.
Accordingly, an object of the present invention is to provide a host microorganism with which production of proteins or polypeptides can be increased through removal of genes which are useless or harmful in the production of proteins or polypeptides from the genome or inactivation of such genes. Another object of the present invention is to provide a recombinant microorganism produced by incorporating, into the above-mentioned host microorganism, a gene which codes for a protein or polypeptide and which is ligated to a transcription initiation regulation region, translation initiation regulation region, or secretion signal region at the downstream end of the region. Yet another object of the present invention is to provide a method for producing a protein or polypeptide by use of the recombinant microorganism.